There has been tremendous recent progress in the area of wearable medical devices capable of monitoring heart conditions, activity levels, respiration rates, and many other physical parameters. However, further progress in this area has been hindered by: 1) large and rigid devices that are not anatomically compliant; and 2) the lack of chemical sensors. The objective of this collaborative project is to develop and demonstrate initial validity of a Flexible Epidermal Multimodal health Monitoring (FlexEM2) system for the simultaneous real- time measurement of multiple key metabolites (sub-dermal glucose, lactate), electrolytes (pH, Na+, Ca2+), electrophysiology (biopotentials - e.g., ECG), and physical parameters (respiration rate, skin temperature), all for use in health status and chronic disease monitoring applications. The combination of multiple sensing modalities into a single wearable platform can yield significant additional insights into the health and physiologica status of individuals compared to what is obtained by monitoring single physical variables alone. By integrating these biosensors on a flexible, epidermal-mounted temporary tattoo-like patch that interfaces directly with ultra-miniaturized wireless electronics, patients can use these devices in ambulatory, outpatient environments with minimal discomfort or obtrusiveness. As a low-cost printed platform that also leverages scaled semiconductor manufacturing, the developed FlexEM2 system can be employed for widespread use as a general diagnostic tool, for preventive healthcare, or for monitoring of patients with chronic health issues such as cancer, congestive heart failure, diabetes, diseases of aging, and obesity. For example, frail elderly patients could be monitored in real-time for early detection of conditions such as dehydration, electrolyte disturbances, hypoglycemia, and cardiac arrhythmias, any of which may precipitate an acute hypotensive episode that in turn may cause a fall, then an injury, then hospitalization or worse. We plan to develop the proposed FlexEM2 system through innovations in printed electrochemical materials on flexible substrates, ultra-low-power bio-instrumentation electronics, and bioelectronic system integration. We will validate the proposed system in in-vitro conditions meant to reflect activities of daily living, first in a healthy population to corrlate newly measured data with data gathered via standard clinical methods. Then we will validate the proposed system in a group of frail elderly patients, also using standard clinical methods.